This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Morphologic brain differences have been identified between children with autism and typically-developing children, though findings have been inconsistent across studies. One potential cause is the variability in brain morphology resulting from the influence of multiple genetic and environmental factors on brain development. A strategy to control for such factors is to compare brain structure between siblings discordant for autism. Specific Aim: To assess the relationship between brain morphology and autism using voxel-based morphometry to examine siblings discordant for autism. Methods: Participants included 27 same-gender sibships consisting of one child with autistic disorder (AU;confirmed with ADI-R and ADOS-G) and one typically-developing sibling (TD). Subjects were between 6-13 years old, and all pairs were less than 4 years apart. High-resolution structural magnetic resonance images were pre-processed (including modulation) and analyzed (paired t-test covarying for age, gender, and total gray/white matter volume) using SPM5 and VBM5.1 (p=0.01 corrected).